Breast CancerPhase 2NATURENCT02725541

Trial of Neoadjuvant Trastuzumab Emtansine in Patients With HER2-Equivocal Breast Cancer

A Phase 2 study testing Trastuzumab emtansine in people with Breast Cancer, run by Jenny C. Chang, MD at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

This is an open label, neoadjuvant phase II study to evaluate the objective response, toxicity, and safety of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast cancer. Trastuzumab emtansine at a dose of 3.6 mg/kg will be intravenously administered every 3 weeks for a total of 6 weeks. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: Trastuzumab emtansine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Mar 2016to May 2019
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female gender;
Age ≥18 years;
Eastern Cooperative Oncology Group performance status of 0-1;
Histologically confirmed invasive breast cancer;
Primary tumor greater than or equal to 1 cm diameter, as measured by clinical examination and mammography or ultrasound;
Any N;

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No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);
HER2 low or equivocal status in the invasive component of the primary tumor (confirmed by a central certified laboratory prior to study entry)
HER2 low expression: 1+/2+ by immunohistochemistry and/or HER2/CEP17 ratio <2.0 with HER2 copy number <6.0 signals/cell
HER2 equivocal expression: HER2 copy number ≥4.0 and <6.0 signals/cell;
Hematopoietic status:
Absolute neutrophil count ≥ 1.0 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin at least 9 g/dL;
Hepatic status: Serum total bilirubin ≤1 x upper limit of normal (ULN; In the case of known Gilbert's syndrome, a higher serum total bilirubin [< 1.5 x ULN] is allowed), Aspartate aminotransferase and alanine aminotransferase ≤1.5 x ULN, Alkaline phosphatase ≤ 1.5 x ULN;
Renal status: Creatinine ≤1.5 mg/dL;
International Normalized Ratio ≤1.5 x ULN;
Baseline left ventricular ejection fraction ≥50%, as measured by echocardiography or multigated acquisition scan;
Negative serum or urine β-human chorionic gonadotropin pregnancy test within 7 days prior study entry for patients of childbearing potential. Women of childbearing potential must use effective contraception (barrier method [condoms, diaphragm] in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, and implantable hormonal contraceptives are not allowed) for the duration of the study and for at least 7 months after the last dose of study treatment;
Signed informed consent form (ICF);
Patient accepts to make available tumor samples for submission to central laboratory to conduct translational studies as part of this protocol.

Who cannot join

Previous (less than 5 years) or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and carcinoma in situ of the cervix;
Patients with a prior malignancy diagnosed more than 5 years prior to study entry;
Preexisting peripheral neuropathy ≥ grade 2;
Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic oxygen therapy;
Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety;
Unresolved or unstable serious adverse events from prior administration of another investigational drug;

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Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy other than the trial therapy);
Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab emtansine or its components;
Ejection fraction <55% or below the lower limit of the institutional normal range;
Pregnant or lactating women;
Concomitant use of cytochrome P450 3A4 inhibitors or inducers;
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol;
Active infection requiring intravenous or oral antibiotics;
Patients unwilling or unable to comply with the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

Houston Methodist Hospital
Houston, Texas, 77030

Other trials in United States

About this study

Read the detailed description

NATURE is an open label, neoadjuvant, phase II study designed to evaluate the objective response rate of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast cancer. Patients will receive trastuzumab emtansine at a dose of 3.6 mg/kg via intravenous infusion every 3 weeks for a total of 6 weeks (2 21-day cycles). Patients who achieve partial or complete response (responders) after the 6-week treatment will continue on trastuzumab emtansine for an additional 12 weeks (4 cycles). The primary objective will be objective response rate after 6 weeks of neoadjuvant trastuzumab emtansine. Secondary objectives will include imaging response (ultrasound and magnetic resonance imaging) after six weeks of neoadjuvant trastuzumab emtansine and toxicity and efficacy of trastuzumab emtansine. After completion of continued trastuzumab emtansine treatment, pathological complete response rate of responders as a whole and according to estrogen receptor status will be explored. Markers related to the mechanism of action of trastuzumab emtansine (HER2 copy number in circulating tumor cells; tissue expression of PTEN, PI3K, and other potential candidate markers) will also be explored.

Conditions: Breast Cancer
Being tested: Trastuzumab emtansine
Keywords: HER2 equivocal, Trastuzumab emtansine, Breast cancer
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Trastuzumab emtansineDrug
Also called ado-trastuzumab emtansine; T-DM1; KADCYCLA
HER2-targeted antibody drug conjugate of trastuzumab and DM1

Study groups in NCT02725541
Study group	Role	What they receive
Experimental	Experimental	Trastuzumab emtansine at a dose of 3.6 mg/kg will be administered via intravenous infusion for 6 weeks (two 21-day cycles). Receives: Drug: Trastuzumab emtansine

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective response rate
Determine the objective response rate after 6 weeks of neoadjuvant trastuzumab emtansine (RECIST 1.1)
Measured: 6 weeks

Secondary outcomes (2)

Radiological response
Determine radiological response after 6 weeks of neoadjuvant trastuzumab emtansine
Measured: 6 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Measured: 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2016May 2019

First posted1 Apr 2016 (estimated)
Study startMar 2016
Primary completionApr 2019 (estimated)
Study completionMay 2019 (estimated)

Why it stopped: loss of funding support

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02725541
Sponsor's protocol ID: Pro00013875
Acronym: NATURE
Status last verified: Sep 2016
First submitted: 18 Mar 2016
Last updated: 14 Sep 2016
Results posted: No
Data monitoring committee: Yes
Individual data sharing: Yes: Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
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All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Trial of Neoadjuvant Trastuzumab Emtansine in Patients With HER2-Equivocal Breast Cancer
ClinicalTrials.gov ID: NCT02725541
Acronym / sponsor ID: NATURE / Pro00013875
Conditions: Breast Cancer
Keywords: HER2 equivocal, Trastuzumab emtansine, Breast cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: loss of funding support
Enrolment: 0 participants (actual)
Lead sponsor: Jenny C. Chang, MDUniversity, hospital or other
Collaborators: Genentech, Inc., The Methodist Hospital Research Institute
Study start: Mar 2016
Primary completion: Apr 2019 (estimated)
Study completion: May 2019 (estimated)
First posted: 1 Apr 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental	Experimental	Drug: Trastuzumab emtansineTrastuzumab emtansine at a dose of 3.6 mg/kg will be administered via intravenous infusion for 6 weeks (two 21-day cycles).

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Female gender;
Age ≥18 years;
Eastern Cooperative Oncology Group performance status of 0-1;
Histologically confirmed invasive breast cancer;
Primary tumor greater than or equal to 1 cm diameter, as measured by clinical examination and mammography or ultrasound;

Key exclusion criteria (16 listed)

Previous (less than 5 years) or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and carcinoma in situ of the cervix;
Patients with a prior malignancy diagnosed more than 5 years prior to study entry;
Preexisting peripheral neuropathy ≥ grade 2;
Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic oxygen therapy;
Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Trastuzumab emtansineAlso: ado-trastuzumab emtansine; T-DM1; KADCYCLAHER2-targeted antibody drug conjugate of trastuzumab and DM1	Drug	Experimental

Primary outcome

Objective response rate
Time frame: 6 weeks
Determine the objective response rate after 6 weeks of neoadjuvant trastuzumab emtansine (RECIST 1.1)

2 secondary outcomes

Radiological response
Time frame: 6 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time frame: 18 weeks

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2016.
Individual participant dataSharing planned: Yes. Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jenny C. Chang, M.D. principal investigator

Houston Methodist Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab emtansine in people with Breast Cancer, run by Jenny C. Chang, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 14 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02725541.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2016.